The overall purpose of this proposal is to determine the risk of developing symptomatic HIV infection and AIDS in a prospective cohort study of at least 200 infants born to seropositive mothers who are intravenous drug abusers or heterosexual partners of drug users. We will follow prospectively children who are born to seropositive mothers and attempt to define biologic and serologic risk factors associated with transmission and to study intensively the natural history of the pediatric infection. Another important goal is to develop virologic and serologic tests and to identify epidemiologic and behavioral risk factors to characterize mothers whose infants have a high risk of developing HIV infection and disease. This will allow us to select targets for prophylaxis or chemotherapy which might prevent infection in infants or might ameliorate such infection. We will also look for biologic differences among strains of HIV, for quantitative differences in the level of leukoviremia, and the differences in antibody responses to viral protein products. In addition, we will use virus isolation, detection of viral antigens and polymerase chair reaction techniques to distinguish, as early in life as possible, infants who are truly infected from those with passive antibodies. These studies combine an active program in the clinical care and surveillance of HIV-infected children with laboratory investigations of HIV biology using contemporary molecular and epidemiologic techniques. The program's strength lies in the ability to combine epidemiologic, clinical, virologic, and molecular biologic approaches for the study of the maternal-infant AIDS problem in one laboratory setting.